Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma

BACKGROUND: Multicentric breast carcinomas have a higher frequency of axillary lymph node metastasis than unifocal tumors of similar stage. It remains unclear whether this merely reflects larger tumor volumes or a different biologic behavior. The authors have shown previously that when aggregate tumor diameter are used for staging, unifocal and multifocal tumors have a similar frequency of axillary lymph node metastasis. However, summing diameter overestimates actual tumor volume because volume is proportional to the third power of the diameter. Therefore, the aim of the current study was to reanalyze the relation between size and axillary lymph node status by correcting for tumor volumes and surface areas. METHODS: Volumes and surface areas of 122 breast tumor specimens with multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n = 5) were calculated by approximating the shape of each tumor nodule to an ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the authors used an internal control series, comprised of 469 macroscopic unifocal tumors. For all patients, multiple assessments of largest tumor size and combined size of all foci were correlated with the status of axillary lymph nodes. The associations between lymph node status, tumor volume or area, and multifocality were modeled using univariate and multivariate logistic regression. RESULTS: When either the largest or the aggregate tumor volume was used as a size estimate, tumor specimens with multiple nodules had a higher frequency of lymph node involvement compared with unifocal tumors of a similar volume or area. The odds ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume measurement (P < 0.001). Surface area estimates yielded similar results (OR = 2.2, P < 0.001). CONCLUSIONS: Breast tumors with multiple macroscopic nodules had a different biology, with a propensity to dissemination at smaller tumor volumes (i.e., there was another factor besides volume alone that accounted for the differences in behavior).     

Multifocal and multicentric breast cancer: does each focus matter?

PURPOSE: The identification of multiple tumors in the breast is associated with increased nodal involvement when compared with similar staged unifocal disease. This study compares two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer. METHODS: The histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995 were examined. Tumors were assessed using two size estimates: (1) largest tumor focus diameter and (2) the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against node positivity. RESULTS: Ninety-four (11.1%) of 848 women had multifocal breast cancer and of these 49 women (52.1%) had axillary node involvement compared with 37.5% with unifocal breast cancer (P =.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Use of this method to stage cancers, rather than the largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas. CONCLUSION: The tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman's disease. This may deny patients the opportunity of adjuvant therapies if the contribution of the smaller foci to the incidence of node positivity and survival is ignored.     

Clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large-format histologic sections

BACKGROUND: Breast carcinoma is a heterogeneous group of diseases deviating from each other not only in their clinical manifestations and outcome but also in their histologic appearance. The submacroscopic morphology of breast carcinomas, the distribution of the lesions, and the extent of the disease are seldom studied. Even more infrequently are these parameters included in surgical pathology reports. Conversely, the routine use of large-format histologic sections in workup of operated breast specimens provides better insight into the significance of these parameters. The aim of the study was to identify breast carcinoma growth patterns indicating increased metastatic potential of the tumor and a need for more aggressive therapy. METHODS: In all, 500 consecutive breast cancer cases, all of which were documented on large-format histologic sections, were retrospectively analyzed. The distribution of both in situ and invasive components of the tumors (unifocal/multifocal/diffuse) was defined, determined, and compared with the type of surgical intervention performed and the frequency of ipsilateral lymph node metastasis as endpoints. The extent of the disease, the size of the tumor, the presence or absence of lymphovascular invasion (LVI), and the proportion of invasive lobular carcinomas in the categories with different distributions were also analyzed. RESULTS: Only 34% of the analyzed cases could be categorized as unifocal. This kind of tumor distribution was associated with lymph node metastasis in 28% of the cases, with LVI in 18%, with breast-conserving surgery in 67%, and with a proportion of 4% invasive lobular carcinomas. Tumors with a unifocal invasive component upgraded to multifocal or diffuse because of the distribution of the associated in situ component had similar characteristics. With their larger extent, tumors with a diffuse in situ component required mastectomy in 43% of cases. Multifocal distribution of the invasive component in the tumors was associated with higher frequency of LVI (42%) and lymph node metastases (48%), with a substantially lower number of cases undergoing breast-conserving surgery (33%) and with a higher proportion of lobular carcinomas (25%). If the multifocal invasive foci were associated with a diffuse in situ component, the proportion of invasive lobular carcinomas was only 5%. The extent of the lesions (defined as the area of breast tissue involved by in situ, invasive, and/or intravascular tumor foci) was >or=2 cm in >90% of multifocal cases and >or=4 cm in >70%. Diffusely growing invasive carcinomas were rare (only 20 cases), but were associated with lymph node metastasis in 60% of cases and resulted in mastectomy in 85% of the cases. Approximately two-thirds (65%) of these tumors belonged to invasive lobular carcinomas. The extent of diffusely growing invasive carcinomas was >or=4 cm in 75% of the cases. Although LVI was detected in only 10% of tumors with a diffusely growing invasive component, such tumors were found to have lymph node metastasis significantly more often (odds ratio of 2.33) and required mastectomy much more frequently (odds ratio of 2.58) compared with purely unifocal breast carcinomas. CONCLUSIONS: These results indicate that the distribution of invasive and in situ tumor structures in breast carcinomas as defined in the current study, together with the extent of disease, are important morphologic parameters which determine the required surgical intervention and are related to biologic factors such as metastatic capacity. The method of large-section histology allows the examiner to properly document and demonstrate these important parameters, thus facilitating understanding of their clinical relevance.     

Early and more advanced unifocal and multifocal breast carcinomas and their molecular phenotypes

Background

I examined the relationship between the recently established prognostic parameter, molecular tumor phenotype and tumor size, lesion distribution (unifocal, multifocal, diffuse growth), and lymph node status.

Materials and Methods

I analyzed 660 consecutive invasive breast carcinomas documented in large-format histology sections. Immunohistochemistry was used to phenotype the tumors on the basis of estrogen and progesterone receptor expression, HER2 (human epithelial growth factor receptor 2) overexpression, and expression of basal markers.

Results

The proportion of luminal A tumors (84.8% vs. 71.6%; P < .0001) and basal-like tumors (5.0% vs. 14.8%; P < .0001) were significantly different in early (<15 mm) and more advanced invasive breast carcinomas, whereas the proportion of luminal B and HER2 type tumors (4.2% vs. 7.8%, and 5.7% vs. 4.8%, respectively) were not. All the phenotypes had similar percentages of multifocal tumors, whereas most diffuse invasive carcinomas were luminal A type. Early luminal A carcinomas had significantly fewer lymph node metastases (LNM) than more advanced carcinomas but luminal B and HER2 type tumors showed no such difference. This difference was evident (15.4% vs. 42.4%) but statistically not significant in the basal-like category. Multifocal tumors of all phenotypes had significantly higher frequencies of LNM compared with unifocal tumors.

Conclusion

Multifocality of the invasive component represents a negative prognostic parameter associated with significantly increased LNM in all phenotype, whereas larger tumor size was such a parameter only in the luminal A category. HER2 overexpression occurs early in the natural history of tumors and is associated with high LNM rates.     

Multifocal breast cancer documented in large‐format histology sections

BACKGROUND:

The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail.

METHODS:

In total, 444 consecutive invasive breast cancers that were documented in large‐format histology slides and worked up with detailed radiologic‐pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes.

RESULTS:

Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14‐fold respectively 2.75‐fold risk of cancer‐related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)‐positive cancers; estrogen receptor‐negative, progesterone receptor‐negative, and HER2‐negative (triple‐negative) cancers; or basal‐like cancers had a 2.18‐fold, 2.33‐fold, and 4.07‐fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2‐positive, and basal‐like cancers were associated with significantly better long‐term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple‐negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant.

CONCLUSIONS:

Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal‐like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters. Cancer 2013. © 2013 American Cancer Society.     

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.      

多灶性甲状腺乳头状癌BRAFv600E基因突变及临床生物学特性分析

探讨多灶性甲状腺乳头状癌不同病灶的BRAFv600E基因突变情况及其临床生物学特性。方法:对86例多灶性与282例单发病灶的甲状腺乳头状癌进行对比,研究其临床生物学特征,并对病灶进行BRAFv600E突变检测分析。结果:86例多灶性甲状腺乳头状癌中,单侧病灶12例,双侧病灶74例;颈部淋巴结转移51例（59.3%）;合并微小癌者46例（53.5%）;合并桥本氏甲状腺炎者23例（26.7%）;局部侵犯10例（11.6%）;发生远处转移者1例（1.2%）;10年生存率91.9%。41.9%的患者所有病灶均有BRAFv600E突变,17.5%均不存在BRAFv600E突变,至少有40.6%的多灶性甲状腺乳头状癌是独立起源的。结论:多灶性甲状腺乳头状癌多发生于双侧甲状腺,合并微小癌及桥本氏甲状腺炎者较多,颈部淋巴结转移及局部侵犯也较多,但远处转移率及10年生存率与单发的甲状腺乳头状癌比较无明显差异,BRAFv600E突变可以间接预测不同病灶的起源问题,且有相当部分多灶性甲状腺乳头状癌的不同病灶是独立起源的。      

Multicentric and multifocal versus unifocal breast cancer: is the tumor-node-metastasis classification justified?

For classification of breast cancer (BC), tumor-node-metastasis (TNM) staging has been considered state of the art for more than 50 years. The T category is well defined, and in multicentric and multifocal tumors, tumor size is assessed by the largest tumor focus. The aim of this study was to compare multicentric/multifocal tumor spread in breast cancer with unifocal disease and to evaluate the diagnostic relevance of multifocality. A retrospective analysis was performed on survival related events in a series of 5,691 breast cancer patients between 1963 and 2007. By matched-pair analysis, patients were entered into two comparable groups of 288 patients after categorizing them as having multifocal/multicentric or unifocal breast cancers. Matching criteria were tumor size, grading, and hormone receptor status, which were equally distributed between both groups (P = 1.000 each). Disease free survival and the occurrence of relapse or of metastatic disease were evaluated. Cox’s regression analysis was used for multivariate analysis. In the unifocal group, the mean breast cancer-specific survival time was 221.6 months as opposed to 203.3 months in the multicentric/multifocal group (P < 0.001, log-rank test). The occurrence of local relapse and distant metastasis was significantly increased in the multifocal group in comparison to the unifocal equivalent group (P < 0.001 and P < 0.003, respectively). Cox regression analysis for multivariate analyses demonstrated focality and centricity to be highly significant predictors for reduced overall survival (P = 0.016), local relapse (P = 0.001) and distant metastasis (P = 0.038). Tumor size, histopathological grading, hormone receptor status, and staging of lymph nodes are well-established prognostic parameters. Additionally, the number of foci should be considered as an independent prognostic parameter, which is currently not reflected in the TNM classification. We conclude that multicentric/multifocal BC is an independent BC risk factor and should be included in the risk assessment by re-evaluating the current TNM classification of the UICC.     

Clinical and pathological features of glycogen-rich clear cell carcinoma of the breast

BACKGROUND: Twenty cases of invasive ductal carcinoma of the breast with a pure or partial glycogen-rich clear cell carcinoma(GRCC)component are reported. GRCC of the breast is composed almost entirely of polygonal cells with clear cytoplasm. These contain large amounts of partly water-soluble glycogen. METHODS: The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, axillary lymph node and Her2/neu status. RESULTS: Between 1990 and 2004, 723 patients with primary breast carcinomas were treated and clinicopathologic analysis was performed. 20 cases were identified as GRCC among the 723 cases. The patients' age at presentation ranged from 33 to 68 years (mean, 52 years). Tumor size ranged from 1 to 6.5 cm (mean, 2.6 cm); 35% (7 of 20) of cases that underwent axillary dissection had positive lymph nodes. Among 15 of 20 cases who were followed for 1-72 months, 5 cases died from their breast carcinoma within 5 years following the diagnosis. CONCLUSION: Our series included more small size carcinomas than did previous series. Lymph node status does not appear to be markedly different from that of the usual invasive ductal carcinomas. Her2/neu expression was similar to that found in common breast carcinomas.     

Immunohistochemical study of Muc1, Muc2 and human gastric mucin in breast carcinoma: relationship with prognostic factors

We investigated the expression of mucin core proteins, Muc1, Muc2, and human gastric mucin (HGM) immunohistochemically in 5 non-invasive, 62 invasive ductal carcinomas and 3 mucinous carcinomas of the breast and statistically examined the relationship with prognostic factors. Muc1 was expressed in almost all breast carcinomas and there was a reverse correlation with tumor size (r = -0.25). However, Muc1 was not significantly correlated with the other tumor characteristics such as lymphocytic infiltration, axillary lymph node metastasis, TNM and plasma levels of CA153. Muc2 and HGM were expressed in 5 cases each in invasive ductal carcinomas, 0 and 3 in non-invasive ductal carcinomas, and 2 and 1 in mucinous carcinomas, respectively. Muc 2 expression correlated with lymph node metastasis. HGM was found in the tumors without lymph node metastasis and lower levels of serum CA153.     

Axillary lymph node metastases associated with small invasive breast carcinomas

BACKGROUND: Over the past 20 years the proportion of invasive breast carcinomas measuring < or = 1 cm has increased progressively. Information regarding the effect of clinical and histologic characteristics on the frequency of lymph node metastases associated with small invasive breast carcinomas is limited. METHODS: A review of Surveillance, Epidemiology, and End Results data was performed using cases diagnosed between January 1988 through December 1993. A total of 12,950 patients with invasive breast carcinomas measuring < or = 1 cm undergoing a resection of the primary tumor and an axillary lymph node dissection were included in this study. The effect of clinical and histologic characteristics on the frequency of lymph node metastases was reviewed. RESULTS: The frequency of lymph node metastases associated with T1a tumors was less than that observed from T1b tumors (9.6% vs. 14.3%; P < 0.001). Tumors with favorable histology (mucinous, papillary, and tubular carcinomas) had a lower frequency of lymph node metastases compared with all other histologic types (3.9% vs. 13.9%; P < 0.001). Increasing histologic grade was associated with an increased risk of lymph node metastases ranging from 7.8% in Grade 1 tumors to 21.0% in Grade 4 tumors (P < 0.001). Increasing patient age was associated with a progressively decreasing frequency of associated axillary lymph node metastases ranging from 22.6% in women age < 40 years to 10.2% in women age > or = 70 years (P < 0.001). CONCLUSIONS: Cases in which an axillary lymph node dissection can be avoided are those with an associated frequency of lymph node metastases < or = 5%, including T1a and T1b mucinous and tubular carcinomas, T1a papillary carcinomas, and T1a Grade 1 carcinomas.     

Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread.     

The effect of tumor size and lymph node status on breast carcinoma lethality

BACKGROUND: It has long been known that both tumor size and the presence of malignant disease in the regional lymph nodes are indicators of outcome for patients with invasive breast carcinoma; however, the way in which these two characteristics could be integrated into an overall assessment of prognosis has not been obvious. METHODS: Kaplan-Meier survival estimates (15 years) according to tumor size and lymph node status were obtained for women with invasive breast carcinoma who were observed at the University of Southern California/Van Nuys Breast Center (Van Nuys, California) or at Massachusetts General Hospital (Boston, Massachusetts). RESULTS: To isolate the individual contributions to death made by tumor size and lymph node status, data were sorted according to both of these variables. For women with tumors of equivalent size, lethality increased with increasing number of positive lymph nodes, such that there was an extra approximately 6% chance of death associated with each positive lymph node. For women with equivalent lymph node status, tumor size was associated with increased lethality, such that each millimeter of tumor diameter was associated with an additional approximately 1% chance of death. The overall lethality was equal to the sum of the contribution from lymph node status and the contribution from tumor size, and this finding led to the creation of a new technique (the Size+Nodes method) for predicting outcome. CONCLUSIONS: The Size+Nodes method was shown to be capable of accurately estimating the risk of death due to invasive breast carcinoma from information on the size of the primary tumor and the number of positive lymph nodes. In addition, this method was used to stratify women into groups according to breast carcinoma lethality. In contrast, classification of women according to lymph node positivity, T status, or disease stage created groups with wide and overlapping levels of lethality.     

Infiltrating breast carcinoma smaller than 0.5 centimeters. Is lymph node dissection necessary?

BACKGROUND: The incidence of axillary lymph node metastases from infiltrating breast carcinomas measuring 1.0 cm or smaller reported in the literature varies from 0% (for tumors measuring < or =0.5 cm) to 27.1% (for all tumors < or =1 cm). METHODS: The authors examined all infiltrating breast carcinomas measuring 1.0 cm or smaller with axillary lymph node dissections in patients seen at their institution between January 1990 and March 1997 (117 cases) to determine the incidence of axillary lymph node metastases. All tumors were evaluated for patient age, histologic type of tumor, modified Bloom-Richardson grade, estrogen and progesterone receptor status, ploidy, S-phase fraction, and angiolymphatic vessel invasion, to determine whether there was a relation between the indicators and axillary lymph node metastases. The authors also performed immunohistochemical stains for the basement membrane components laminin and Type IV collagen on the tumors demonstrating metastases and on an equal number of size- and date-matched tumors not demonstrating metastases. RESULTS: Twelve cases of infiltrating carcinoma with axillary lymph node metastases were identified (a 10.3% overall incidence of metastases). Lymph node metastases were not identified in any of the cases with tumors measuring < or =0.5 cm (24 cases). The incidence of axillary lymph node metastases for carcinomas 0.6-1.0 cm was 12.9% (12 of 93 cases). High nuclear grade was found to correlate with the presence of lymph node metastases (P = 0.007). No statistically significant correlation was found between the other indicators examined and axillary lymph node metastases or between basement membrane staining and axillary lymph node metastases. CONCLUSIONS: The authors concluded that infiltrating breast carcinomas measuring < or =0.5 cm are unlikely to have demonstrable axillary lymph node metastases. Lymph node dissections in these women may be unnecessary. Nuclear grade may be the best predictor of lymph node metastases in T1b tumors.     

乳腺癌腋窝淋巴结转移血管生成的免疫组化研究

目的　研究乳腺癌腋窝淋巴结转移的血管生成情况。方法　采用内皮细胞ⅧFRAg 免疫组化染色技术,对37 例乳腺癌根治术或改良根治术切除的乳腺癌组织和121 枚腋窝转移淋巴结进行免疫组化染色。在100 倍视野下通过显微电视系统计数微血管密度( MVD) ,并用显微测量器测量转移灶的直径。结果　在121 个淋巴结中找到13 处微转移灶,其平均直径为(210 ±37) μm ,无血管生成。腋窝淋巴结转移瘤的MVD 为89-3 ±18-4 ,与乳腺癌组织MVD(93-8 ±21-8) 差异无显著性,且微血管分布不均,周围高于中央。结论　淋巴结微转移灶无血管生成,转移瘤有血管生成。为抑制微转移灶发展成转移瘤,以及抑制转移瘤的生长,抑制血管生成可能是控制淋巴结转移的有效措施。     

Characterisation of multifocal breast cancer using the 70-gene signature in clinical low-risk patients enrolled in the EORTC 10041/BIG 03-04 MINDACT trial

BackgroundIn multifocal breast cancer, guidelines recommend basing adjuvant systemic treatment decisions on characteristics of the largest lesion, disregarding multifocality as an independent prognosticator. We assessed the association between multifocal disease and both the 70-gene signature (70-GS), and distant metastasis-free survival (DMFS) in clinical low-risk breast cancer patients enrolled in the European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy (MINDACT) trial.Patients and methodsThe analysed population consisted of enrolled patients in the MINDACT trial with clinical low-risk disease, defined by a modified Adjuvant! Online cut-off for the 10-year risk of recurrent disease or death. Eligibility criteria of MINDACT dictate that patients with multifocal disease could be included if the different lesions had similar pathological characteristics. The presence of multifocal disease was deducted from the case report form (CRF)-question for sum of diameter for all invasive tumour foci. Clinicopathological characteristics and gene expression of patients with unifocal and multifocal (largest lesion) disease were compared. Subsequently, the association between multifocal disease and the 70-GS was evaluated as well as the association between multifocality and 5-year DMFS.ResultsThe study included 3090 clinical low-risk patients with unifocal and 238 patients with multifocal disease. Apart from a higher prevalence of lobular tumours (21.8% versus 10.8%, by local pathology), we did not observe differences in baseline characteristics between multifocal and unifocal tumours. Patients with multifocal tumours were more likely to be at high genomic risk as compared to patients with unifocal tumours (22.7% versus 17.3%, odds ratio [OR] 1.45, 95% confidence interval [CI] 1.02–2.07, P = 0.038). We did not find a significant association between tumour focality and DMFS (97.1% for unifocal versus 96.9% for multifocal, hazard ratio [HR] = 1.55, 95% CI 0.68–3.46, P = 0.172), nor a signal for a potential interaction between the prognostic effect of the 70-GS and focality of the tumour regarding DMFS.ConclusionIn the group of clinical low-risk MINDACT patients, multifocal tumours were more likely to have a high-risk 70-GS profile compared to unifocal tumours. We did not observe a significant interaction between multifocality and the 70-GS with respect to survival without distant metastasis in these patients.     

Sentinel node biopsy in patients with multiple breast cancer

BACKGROUND: Multicentric or multifocal breast cancer is considered a limitation for sentinel lymph node biopsy (SLNB). Studies showing that all quadrants of the breast drain via common afferent lymphatic channels indicate that multiple tumors do not affect lymphatic drainage. We therefore assessed the accuracy of SLNB in patients with multiple breast tumors. METHODS: Of the 942 breast cancer patients who underwent SLNB using radioisotope at Asan Medical Center between January 2003 and December 2006, 803 had unifocal and 139 had multiple tumors. Axillary dissection after SLNB was performed on 884 patients, 757 with unifocal and 127 with multiple tumors. All patients underwent lymphatic scintigram for removal of sentinel lymph nodes (SLNs). The clinical characteristics and accuracy of SLNB was compared in patients with unifocal and multiple breast cancer. RESULTS: In the multiple tumor group, 2.68 +/- 0.84 SLNs were identified in 136 of 139 patients (identification rate, 97.84%); 81.5% of SLNs were identified by scintigram. The incidence of axillary metastases was 29.50% (41/139). SLNB accuracy was 97.63% (124/127), with a false negative (FN) rate of 7.89% (3/38). In the unifocal group, 2.67 +/- 0.96 SLNs were identified in 787 of 803 patients (identification rate, 98.00%); 84.8% of SLNs were identified by scintigram. The incidence of axillary metastasis was 22.04% (177/803). SLNB accuracy was 98.02% (742/757), with a FN rate of 8.62% (15/174). The accuracy and FN rate of SLNB did not differ significantly between unifocal and multiple breast cancer. CONCLUSION: The accuracy of SLNB in multiple breast cancer is comparable to its accuracy in unifocal cancer. These findings indicate that SLNB can be used an as alternative to complete axillary lymph node dissection in patients with multiple breast tumors.     

Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1-related breast carcinoma

BACKGROUND: A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas. METHODS: The relation between the greatest dimension of the resected breast tumor (size) and the presence of positive axillary lymph nodes (expressed as a percentage of all lymph nodes examined) was evaluated in 1555 women with invasive breast carcinoma who were ascertained at 10 centers in North America between 1975 and 1997. There were 276 BRCA1 mutation carriers, 136 BRCA2 carriers, and 1143 women without a known mutation (208 BRCA1/BRCA2 noncarriers and 935 untested women). Patients were stratified according to tumor size, and odds ratios were estimated for the presence of positive lymph nodes with increasing tumor size. RESULTS: A highly significant positive correlation between tumor size and the frequency of positive axillary lymph nodes was seen for BRCA1/BRCA2 noncarriers, for BRCA2 carriers, and for untested women (overall P < 0.0001 for each). In contrast, there was no clear correlation between tumor size and positive lymph node status in BRCA1 carriers (overall P = 0.20). CONCLUSIONS: The relation between tumor size and lymph node status in patients with breast carcinoma appears to be different in BRCA1 carriers compared with BRCA2 carriers and noncarriers. These findings have important implications for estimating the route of metastatic spread and for evaluating the effectiveness of early diagnosis in patients with BRCA1-related breast carcinoma.     

Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer.

PURPOSE: To examine the prognostic significance of lumican and decorin, two abundant small leucine-rich proteoglycans in breast tissue stroma. EXPERIMENTAL DESIGN: Lumican and decorin expression was examined in a cohort of 140 invasive breast carcinomas by Western blot analysis. All cases were axillary lymph node-negative and treated by adjuvant endocrine therapy. RESULTS: Lumican and decorin expression was highly correlated (r = 0.45, P < 0.0001), but although low levels of lumican were associated with large tumor size (P = 0.0496), negative estrogen receptor (P = 0.0024) and progesterone receptor status (P = 0.0116), and increased host inflammatory response (P = 0.0077), low decorin levels were associated only with large tumor size (P = 0.0496). However, using univariate analysis, low levels of lumican and decorin were both associated with a shorter time to progression (P = 0.0013 and 0.0262) and poorer survival (P = 0.001 and 0.0076). In multivariate analysis using the Cox regression model, low decorin was also shown to be an independent predictive factor for recurrence (hazard ratio 2.25: 95% confidence interval 1-5, P = 0.047) and survival (hazard ratio 3.39: 95% confidence interval 1.2-9.6, P = 0.021). CONCLUSIONS: These results suggest that low levels of small leucine-rich proteoglycans in breast tumors may be associated with a worse prognosis in lymph node-negative invasive breast carcinomas and warrant further study with larger patient cohorts.     

乳腺癌骨转移相关的临床病理因素的研究

目的：研究与乳腺癌骨转移有关的临床、病理因素，探讨有助于预测乳腺癌骨转移的危险因素。方法：对本院1981年1月～2000年12月手术的3796例乳腺癌患者的随访资料进行回顾分析，根据首发转移部位分组，研究116例骨转移的临床、病理资料，并与内脏转移、淋巴结或软组织转移患者的情况作比较。结果：本组病例首次复发为骨转移者116例，占3．1％；骨转移与患者年龄轻、肿块直径大、临床体检腋淋巴结肿大、腋淋巴结转移数多、病期为Ⅱ／Ⅲ期、组织学类型为非特殊型浸润性癌相关；多因素逐步回归分析术前资料显示，肿块大小、体检腋淋巴结状况与骨转移相关；术后资料中，肿块大小、腋淋巴结转移数、病理类型与骨转移相关。本组骨转移患者均曾接受正规的局部治疗和辅助化疗；首次复发在局部、淋巴结、软组织或局部复发伴远处转移组中，特殊型浸润性癌所占比例明显高于骨转移的患者；骨转移和内脏转移的时间分布无差别，而局部复发和／或淋巴结、软组织转移组，复发时间较骨转移组早。结论：年轻的、肿块分级为T2／T3，临床体检腋淋巴结肿大者，术前有必要进行同位素骨扫描检查；非特殊型浸润性乳腺癌，肿块分级为T2／T3，腋淋巴结转移数≥4枚，为骨转移的高危因素，可在此类病例中开展双磷酸盐的辅助治疗研究。